Background: Hepatobiliary cystadenocarcinoma is a rare epithelial malignant neoplasm of the liver or extrahepatic bile ducts. Early diagnosis of hepatobiliary cystadenocarcinoma is difficult because of its asymptomatic features and rarity. Moreover, the molecular pathogenesis of hepatobiliary cystadenocarcinoma remains unclear. Herein, we described a case of hepatobiliary cystadenocarcinoma in female with chronic hepatitis B and repeated hepatolithiasis. Case presentation: A 65-year-old woman with medical history of latent hepatitis B virus infection, repeated choledocholisthiasis, and cholecystitis was admitted due to a heterogeneous cystic mass (5.6 cm × 4 cm) shown on abdominal ultrasonography during regular physical checkup. The patient complained about irregular bowel movements with intermittent diarrhea for two months before presentation. Computed tomography (CT) disclosed a multiloculated cystic lesion in the left hepatic lobe with the presence of intraductal stones and dilatation of intrahepatic ducts. Histological results obtained from left lobectomy specimens showed hepatobiliary cystadenocarcinoma without accompanied mesenchymal stroma. Conclusion: Notably, hepatobiliary cystadenocarcinoma without mesenchymal stroma seldom occurs in women and is usually associated with poor prognosis. We present the rare findings in this patient and suggest that chronic inflammatory insults in the intrahepatic bile ducts might shed light on the cystadenocarcinogenesis.